A Phase II Study of AMT-676 Combination Therapies in Advanced Colorectal Cancer

Official title

An Phase II Study Evaluating the Safety and Efficacy of AMT-676 in Combination With 5-fluorouracil, Leucovorin, Bevacizumab (or Cetuximab) in Participants of Advanced Colorectal Cancer

Overview

This study is an open, multi-center, phase II study, aiming to evaluate the safety, tolerability and efficacy of AMT-676 combined with 5-fluorouracil, leucovorin, bevacizumab (or cetuximab) in participants with advanced colorectal cancer, and to assess the PK(Pharmacokinetic) characteristics and immunogenicity of AMT-676.

Interventions

• Drug AMT-676
  Patients will get different dose levels treatment of AMT-676. AMT-676 will be Administered as an intravenous (IV) infusion every 2 weeks (Q2W) or every 4 weeks (Q4W).
• Drug 5-FU
  5-FU 400 mg/m\^2 IV bolus on day 1, followed by 1200 mg/m\^2/day x 2 days (total 2400 mg/m\^2 over 46-48 hours) IV continuous infusion, q2w
• Drug Leucovorin
  Leucovorin 400 mg/m\^2 IV day 1, q2w
• Drug Bevacizumab
  Bevacizumab 5 mg/kg IV, day 1
• Drug Cetuximab
  Cetuximab 500 mg/m\^2 IV over 2 hours, day 1, q2w
• Drug Irinotecan
  Irinotecan 180 mg/m\^2 IV, day 1
• Drug Oxaliplatin
  Oxaliplatin 85 mg/m\^2 IV, day 1

Primary outcome measures

• AE & SAE [Time frame: 30 days after the last treatment]
• MTD [Time frame: 28 days after first dose]
• DLTs [Time frame: 28 days after first dose]
• ORR [Time frame: through study completion, an average of 18 months]
• PFS [Time frame: through study completion, an average of 18 months]

Secondary outcome measures (5)

• Cmax [Time frame: From first dose to end of treatment, an average of 1 year]
• Ctrough [Time frame: From first dose to end of treatment, an average of 1 year]
• AUC [Time frame: From first dose to end of treatment, an average of 1 year]
• Specification of anti-drug antibodies [Time frame: From first dose to end of treatment, an average of 1 year]
• Quantification of anti-drug antibodies [Time frame: From first dose to end of treatment, an average of 1 year]

Eligibility criteria

Inclusion criteria

• Patients must be willing and able to sign the ICF, and to adhere to the study visit schedule and other protocol requirements
• Patients with pathologically confirmed, unresectable advanced colorectal adenocarcinoma
• Patients must have at least one measurable lesion as per RECIST version 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Life expectancy ≥6 months
• Patients must have adequate organ function
• Male and female individuals with child bearing potential must agree to take effective contraceptive measures from the moment they sign the informed consent form until 6 months after the last administration of the study drug
• WCBP(Women of Child-Bearing Potential) must have a negative serum pregnancy test within 7 days prior to first dose of the IMP
• Male patients must agree not to donate sperm, and female patients must agree not to donate eggs, while on study treatment and for at least 3 months and 6 months, respectively, after the last dose of the IMP(Investigational Medicinal Product)
• Availability of tumor tissue sample

Exclusion criteria

• Prior treatment with any same target
• Systemic anti-neoplastic therapy within five half-lives or 21 days, whichever is shorter, prior to first dose of the IMP
• Persistent toxicities from previous systemic anti-neoplastic treatments of Grade >1
• Major surgery within 28 days prior to first dose of the IMP, or no recovery from side effects of such intervention, or a surgery is planned to be conducted within the expected participation period of the trial or within 4 weeks after the last administration of the drug
• History of thromboembolic or cerebrovascular events during last 6 mouths
• During the three months prior to the first administration of the drug, there were any life-threatening bleeding events, or grade 3 or higher gastrointestinal/venous variceal bleeding events that required blood transfusion, endoscopy, or surgical treatment. Or there were other diseases that the researchers believed posed a higher risk of bleeding or thrombosis during the study period
• Has a history of interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis , or other lung disease significantly impacting lung function at baseline.
• Any other concurrent diseases or conditions that could affect the research judgment or impede the completion of the research procedures and follow-up checks
• Central nervous system (CNS) metastasis
• Have a history of active or acute diverticulitis, abdominal abscess, gastrointestinal obstruction, fistula, or peritoneal cancer
• Any evidence indicates severe or uncontrolled systemic diseases
• Acute and/or clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV).
• Administration of a live vaccine within 28 days prior to the administration of the first dose of the IMP
• Patients requiring concurrent treatment of strong/moderate inhibitors or strong inducers of cytochrome P450 3A4 or 1A2 enzyme (CYP3A or CYP1A2) within 2 weeks prior to the first dose and during the study treatment
• Known or suspected severe allergy/hypersensitivity (resulting in treatment discontinuation) to monoclonal antibodies
• Known or suspected intolerance to the components of the IMP
• Concurrent participation in another investigational therapeutic clinical trial
• Pregnant or breast-feeding females
• Investigator determined that the trial participants who were not suitable to participate in this study for other reasons

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07474727 · AMT-676-201

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗